US3799936A - Unsymmetrical esters of 1,4-dihydropyridine 3,5-dicarboxylates - Google Patents
Unsymmetrical esters of 1,4-dihydropyridine 3,5-dicarboxylates Download PDFInfo
- Publication number
- US3799936A US3799936A US00242238A US24223872A US3799936A US 3799936 A US3799936 A US 3799936A US 00242238 A US00242238 A US 00242238A US 24223872 A US24223872 A US 24223872A US 3799936 A US3799936 A US 3799936A
- Authority
- US
- United States
- Prior art keywords
- ester
- acid
- dihydropyridine
- methyl
- allyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
- C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
Definitions
- the compounds of which 2,6-dimethyl- 4 (2' methyl phenyl) 1,4 dihydropyridine 3,5-dicarboxylic acid 3-methyl-5-allyl ester is a typical example, can be prepared through condensation of an ylidene-flketocarboxylic acid ester with either an enamino carboxylic acid ester or a s-ketocarboxylic acid ester and ammonia.
- the present invention relates to unsymmetrical esters of 1,4-dihydropyridine-dicarboxylic acids, to processes for their production and to their use as coronary and antihypertensive agents.
- esters of 4-substituted-1,4-dihydropyridine 3,5 dicarboxylic acids are known [see for example Knoevenagel, Ber. 31, 743 (1898) and US. Pats. Nos. 3,325,505; 3,441,648; 3,485,847; 3,488,359 and 3,511,847], all of these have been symmetrical with respect to the ester groups in the 3- and S-positions. Indeed up to the present, the preparative methods available to the art for such esters were limited to the preparation of symmetrical esters.
- the present invention is directed at compounds of the formula:
- R is phenyl, unsubstituted or substituted by up to three substituents selected from the group consisting of lower alkyl, lower alkoxy, halogeno, trifluoromethyl or carbo- (lower alkoxy);
- R and R independent of the other, is hydrogen or lower alkyl
- R is a member selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, or lower alkoxy(lower alkyl);
- R is a member different from R selected from the group consisting of lower alkenyl, lower alkynyl or lower alkoxy(lower alkyl),
- alkyl denotes a univalent saturated branched or straight hydrocarbon chain containing from 1 to 18 carbon atoms.
- Representative of such alkyl groups are thus methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec.- butyl, tert.butyl, pentyl, isopentyl, neopentyl, tertpentyl, hexyl, isohexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, and the like.
- lower alkyl denotes a univalent saturated branched or straight hydrocarbon chain containing from 1 to 6 carbon atoms.
- Representative of such lower alkyl groups are thus methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec.butyl, tert.butyl, pentyl, isopentyl, neopentyl, tert.pentyl, hexyl, and the like.
- lower alkenyl denotes a univalent branched or straight hydrocarbon chain containing from 2 to 6 carbon atoms and nonterminal ethylenic unsaturation as, for example, vinyl, allyl, isopropenyl, 2-butenyl, B-methyl- 2-butenyl, 2-pentenyl, 3-pentenyl, Z-hexenyl, 4-hexenyl, and the like.
- lower alkynyl denotes a univalent branched or straight hydrocarbon chain containing from 2 to 6 carbon atoms and nonterminal acetylenic unsaturation as, for example, ethynyl, 2-propynyl, 4-pentylnyl, and the like.
- the present invention also pertains to the physiologically acceptable non-toxic acid addition salts of these basic compounds.
- Such salts include those derived from organic and inorganic acids such as, without limitation, hydrochloric acid, hydrobromic acid, phos-.
- the compounds of the present invention can exist as optical isomers and both the racemates of these isomers and the individual isomers themselves are within the scope of the present invention.
- the racemates can be separated into their individual isomers through the well known technique and forming diastereoisomeric salts with optically active acids.
- the compounds of the present invention are valuable cardiovascular agents possessing in particular coronary vascular dilation properties together with antihypertensive properties.
- RCH C with either (a.) an enaminocarboxylic acid ester of the formula:
- Typical compounds of the present invention include:
- the compounds of this invention are valuable cardiovascular agents.
- the compounds upon administration cause a distinct and longlasting dilation of the coronary vessels with a simultaneous nitrite-like reduction on the workload of the heart.
- an antifibrillation effect and spasmolytic activity can be observed, the latter often manifesting itself not only in the smooth vascular muscle but also in the smooth muscle of the stomach, intestinal tract, urogenital tract and respiratory system.
- the compounds also exhibit hypotensive properties in the normoand hypertonic animal.
- the dose administered must of course be carefully adjusted to the age, weight and condition of the individual being treated, as well as the route of administration, dosage form and regimen, and the result desired. A satisfactory result can, in certain instances, be obtained at a dose as low as 0.0005 mg./kg. iv. and 0.01 mg/kg. p.o.
- the upper limit of the dosage range is about 10 mg./kg. i.v. and mg./kg. p.o.
- Preferred ranges are from about 0.001 to about 1 mg./kg. i.v. and from about 0.1 to about 10 mg./kg. p.o.
- the compounds of the present invention are administered parenterally or orally in any of the usual pharmaceutical forms.
- These include solid and liquid oral unit dosage forms such as tablets, capsules, powders, suspensions, solutions, syrups and the like, including sustained release preparations, and fluid injectable forms such as sterile solutions and suspensions.
- unit dosage form as used in this specification and the claims refer to physically discrete units to be administered in single or multiple dosage to animals, each unit containing a predetermined quantity of active material in association with the required diluent, carrier or vehicle.
- the quantity of active material is that calculated to produce the desired therapeutic efiect upon administration of one or more of such units.
- Powders are prepared by comminuting the compound to a suitable fine size and mixing with a similarly comminuted diluent pharmaceutical carrier such as edible carbohydrate material as for example, starch. Sweetening, flavoring, preservative, dispersing and coloring agents can also be present.
- a similarly comminuted diluent pharmaceutical carrier such as edible carbohydrate material as for example, starch. Sweetening, flavoring, preservative, dispersing and coloring agents can also be present.
- Capsules are made by preparing a powder mixture as described above and filling formed gelatin sheaths.
- a lubricant such as talc, magnesium stearate and calcium stearate can be added to the powder mixture as an adjuvant before the filling operation;
- a glidant such as colloidal silica may be added to improve flow properties;
- a disintegrating or solubilizing agent may be added to improve the availability of the medicament when the capsule is ingested.
- Tablets are made by preparing a powder mixture, granulating or slugging, adding a lubricant and disintegrant and pressing into tablets.
- a powder mixture is prepared by mixing the compound, suitably comminuted, with a diluent or base such as starch, sucrose, kaolin, dicalcium phosphate and the like.
- the powder mixture can be granulated by wetting with a binder such as syrup, starch paste, acacia mucilage or solutions of cellulosic or polymeric materials and forcing through a screen.
- a binder such as syrup, starch paste, acacia mucilage or solutions of cellulosic or polymeric materials and forcing through a screen.
- the powder mixture can be run through the tablet machine and the resulting imperfectly formed slugs broken into granules.
- the granules can be lubricated to prevent sticking to the tablet forming dies by means of the addition of stearic acid, a stearate salt, talc or mineral oil.
- the lubricated mixture is then compressed into tablets.
- the medicaments can also be combined with free flowing inert carriers and compressed into tablets directly without going through the granulating or slugging steps.
- a protective coating consisting of a sealing coat of shellac, a coating of sugar or polymeric material and a polish coating of Wax can be provided.
- Dyestuffs can be added to these coatings to distinguish different unit dosages.
- Oral fluids such as syrups and elixirs can be prepared in unit dosage form so that a given quantity, e.g., a teaspoonful, contains a predetermined amount of the compound.
- Syrups can be prepared by dissolving the compound in a suitably flavored aqueous sucrose solution while elixirs are prepared through the use of a nontoxic alcoholic vehicle.
- Suspensions can be formulated by dispersing the compound in a nontoxic vehicle in which it is insoluble.
- Fluid unit dosage forms for parenteral administration can be prepared by suspending or dissolving a measured amount of the compound in a nontoxic liquid vehicle suitable for injection such as an aqueous or oleaginous medium and sterilizing the suspension or solution.
- a nontoxic liquid vehicle suitable for injection such as an aqueous or oleaginous medium
- a measured amount of the compound is placed in a vial and the vial and its contents are sterilized and sealed.
- An accompanying vial or vehicle can be provided for mixing prior to administration.
- compositions of the invention can also contain other nontoxic adjuvants and modifiers such as dyes, buffering agents, preservatives, surfactants, emulsifiers, such as nonionic and anionic emulsifiers as, for example, polyoxyethylene-fatty acid esters, polyoxyethylene-fatty alcohol ethers, alkylsulphonates and arylsulphonates, or dispersing agents as, for example, lignin, sulfite waste lyes, methylcellulose, starch and polyvinyl pyrrolidone, perfumes, flavoring agents, preservatives and biocides.
- nontoxic adjuvants and modifiers such as dyes, buffering agents, preservatives, surfactants, emulsifiers, such as nonionic and anionic emulsifiers as, for example, polyoxyethylene-fatty acid esters, polyoxyethylene-fatty alcohol ethers, alkylsulphonates and arylsulphonates, or dispersing agents as,
- compositions adapted for oral administration employ such ingredients as diluents and carriers, excipients and lubricants, as glucose, lactose, sucrose, corn and potato starch, sodium carboxymethyl cellulose, ethyl cellulose, cellulose acetate, powdered gum tragacanth, gelatin, alginic acid, agar, stearic acid, sodium, calcium and magnesium stearates, sodium lauryl sulfate, polyvinylpyrrolidone, sodium citrate, calcium carbonate, and dicalcium phosphate.
- diluents and carriers excipients and lubricants
- glucose, lactose, sucrose, corn and potato starch sodium carboxymethyl cellulose, ethyl cellulose, cellulose acetate, powdered gum tragacanth, gelatin, alginic acid, agar, stearic acid, sodium, calcium and magnesium stearates, sodium lauryl sulfate, polyviny
- compositions adapted for parenteral injection employ such diluents and carriers as water and water-miscible organic solvents, in particular sesame oil, groundnut oil, aqueous propylene glycol, and N,N-dimethylformamide.
- diluents and carriers as water and water-miscible organic solvents, in particular sesame oil, groundnut oil, aqueous propylene glycol, and N,N-dimethylformamide.
- examples of pharmaceutical compositions of the invention adapted for parenteral administration include sterile isotonic saline aqueous solutions of the active ingredient, which can be bufiered with a. pharmaceutically acceptable buffer and are preferabl pyrogen free.
- EXAMPLE 4 Boiling a solution of 14.3 g. of 2'-trifluoromethylbenzylideneacetoacetic acid ethyl ester and 7.0 g. of fl-aminocrotonic acid propargyl esterin 50 m1. of ethanol for 10 hours yielded 2,6-dimethyl-4-(2'-trifluoromethylphenyl)- l,4-dihydropyridine-3,S-dicarboxylic acid 3-ethyl ester-5- propargyl ester of melting point 130 (from ethanol). Yield 49% of theory.
- EXAMPLE 14 By 8 hours heating of a solution of 12.6 g. 2-chlorobenzylidene acetoacetic acid ethyl ester, 8.0 g. acetoacetic acid-B-methoxyethyl ester and 6 ml. ammonia in 80 ml. ethanol under reflux, 2,6-dimethyl-4-(2'-chlorophenyl)- 1,4-dihydropyridine 3,5-dicarboxylic acid 3-[3-methoxyethyl ester S-ethyl ester of melting point 107l08 C. (acetic ester/petroleum ether) was obtained. Yield 54% of theory.
- EXAMPLE 15 By 8 hours boiling of a solution of 15.0 g. 3'-trifluoromethylbenzylideneacetoacetic acid isopropylester and 7.1 g. amino-crotonic acid allyl ester in 80 ml. ethanol, 2,6- dimethyl-4-(3-trifluoromethyl phenyl) 1,4 dihydropyridine-3,5-dicarboxylic acid 3-isopropyl ester 5-allyl ester of melting point 99-100 C. (acetic ester/petroleum ether) was obtained. Yield 52% of theory.
- EXAMPLE 18 Atfer 10 hours boiling of a solution of 12.4 g. 2'- methoxybenzylidene acetoacetic acid ethyl ester, 7.0 g. acetoacetic acid ethyl ester, 7.0 g. acetoacetic acid propargyl ester and 6 ml. conc. ammonia in '60 ml. propan-2 ol, 2,6-dimethyl-4-(2 methoxyphenyl) 1,4-dihydropyridine 3,5 dicarboxylic acid 3-propargyl ester -ethyl ester of melting point 113-1l4 C. (acetic ester/petroleum ether) was obtained. Yield 47% of theory.
- EXAMPLE 19 After 8 hours heating of a solution of 15.0 g. 4'-carboxyethylbenzylidene acetoacetic acid propargyl ester and 6.5 g. amino-crotonic acid ethyl ester in 50 ml. ethanol, 2,6 dimethyl 4 (4' carboxyethylphenyl) 1,4 dihydropyridine-3,S-dicarboxylic acid 3-propargyl ester S-ethyl ester of melting point 110 C. (ethanol) was obtained. Yield 55% of theory.
- R is lower alkyl and R is allyl, propargyl or lower alkoxy(lower alkyl).
- R and R are each methyl, R is methyl, ethyl, propyl or isopropyl, R is allyl, propargyl, methoxyethyl or propoxyethyl and R is phenyl substituted by methyl, methoxy, fiuoro, chloro, trifluoromethyl or carbo(lower alkoxy).
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
- Pyridine Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE2117572A DE2117572C3 (de) | 1971-04-10 | 1971-04-10 | Unsymmetrische 1,4-Dihydropyridin ^-dicarbonsäureester, Verfahren zu ihrer Herstellung sowie ihre Verwendung als Arzneimittel |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US05/399,387 Division US3932646A (en) | 1971-04-10 | 1973-09-21 | Pharmaceutical compositions containing unsymmetrical esters of 1,4-dihydropyridine 3,5-dicarboxylate |
Publications (1)
Publication Number | Publication Date |
---|---|
US3799936A true US3799936A (en) | 1974-03-26 |
Family
ID=5804434
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US00242238A Expired - Lifetime US3799936A (en) | 1971-04-10 | 1972-04-07 | Unsymmetrical esters of 1,4-dihydropyridine 3,5-dicarboxylates |
Country Status (27)
Country | Link |
---|---|
US (1) | US3799936A (fr) |
JP (1) | JPS5527054B1 (fr) |
AT (1) | AT316552B (fr) |
AU (1) | AU459338B2 (fr) |
BE (1) | BE781879A (fr) |
BG (4) | BG20106A3 (fr) |
CA (1) | CA925513A (fr) |
CH (2) | CH571493A5 (fr) |
CS (2) | CS177821B2 (fr) |
DD (1) | DD104519A5 (fr) |
DE (1) | DE2117572C3 (fr) |
DK (1) | DK132321C (fr) |
ES (1) | ES401615A1 (fr) |
FI (1) | FI55187C (fr) |
FR (1) | FR2132831B1 (fr) |
GB (1) | GB1331405A (fr) |
HU (1) | HU165875B (fr) |
IE (1) | IE36947B1 (fr) |
IL (1) | IL39170A (fr) |
LU (1) | LU65129A1 (fr) |
NL (1) | NL170140C (fr) |
NO (1) | NO133711C (fr) |
PL (2) | PL84571B1 (fr) |
RO (2) | RO59959A (fr) |
SE (1) | SE371824B (fr) |
SU (2) | SU431671A3 (fr) |
ZA (1) | ZA722355B (fr) |
Cited By (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3857849A (en) * | 1973-02-28 | 1974-12-31 | Bayer Ag | 2-amino-1,4-dihydropyridine derivatives |
US3862162A (en) * | 1972-08-31 | 1975-01-21 | Bayer Ag | Certain-2-amino-1,4-dihydro-4-phenyl-6-lower alkyl (or phenyl)-3-pyridinecarboxylates |
US3867393A (en) * | 1972-03-06 | 1975-02-18 | Horst Meyer | 2-Amino-1,4-dihydropyridine derivatives |
US3876646A (en) * | 1972-03-06 | 1975-04-08 | Bayer Ag | 2-amino-4,5-dihydropyridine derivatives |
US3883540A (en) * | 1972-03-06 | 1975-05-13 | Bayer Ag | Unsymmetrical esters of N-substituted 1,4-dihydropyridine 3,5-dicarboxylic acid |
US3887558A (en) * | 1972-03-06 | 1975-06-03 | Bayer Ag | Process for producing 2,6-diamino -1,4- dihydro-3,5-pyridine-dicarboxylates and derivatives thereof |
US3905983A (en) * | 1972-09-30 | 1975-09-16 | Bayer Ag | 3,5,6-Tricarboxy- and 2,3,5,6-tetracarboxy-1,4-dihydropyridine derivatives |
US3917619A (en) * | 1972-03-06 | 1975-11-04 | Bayer Ag | 2-Amino-4,5-dihydropyridine derivatives |
US3917620A (en) * | 1972-03-06 | 1975-11-04 | Bayer Ag | 2-Amino-4,5-dihydropyridine derivatives |
US3917622A (en) * | 1972-03-06 | 1975-11-04 | Bayer Ag | 2-Amino-1,4-dihydropyridine derivatives |
US3920823A (en) * | 1972-03-06 | 1975-11-18 | Bayer Ag | Use of unsymmetrical esters of n-substituted 1,4-dihydropyridine 3,5-dicarboxylic acid as cardio-vascular agents |
US3935223A (en) * | 1972-03-06 | 1976-01-27 | Bayer Aktiengesellschaft | 2-Amino-1,4-dihydropyridine derivatives |
US3939171A (en) * | 1972-03-06 | 1976-02-17 | Bayer Aktiengesellschaft | 2-Amino-1,4-dihydropyridine derivatives |
US3988458A (en) * | 1972-03-06 | 1976-10-26 | Bayer Aktiengesellschaft | Bicyclic derivatives of 1,4-dihydropyridine 3,5-carboxylic acid esters |
US3989708A (en) * | 1972-08-31 | 1976-11-02 | Bayer Aktiengesellschaft | 2-Amino-1,4-dihydropyridine derivatives |
US4001258A (en) * | 1972-03-06 | 1977-01-04 | Bayer Aktiengesellschaft | 2-amino-1,4-dihydropyridine derivatives |
US4264611A (en) * | 1978-06-30 | 1981-04-28 | Aktiebolaget Hassle | 2,6-Dimethyl-4-2,3-disubstituted phenyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid-3,5-asymmetric diesters having hypotensive properties, as well as method for treating hypertensive conditions and pharmaceutical preparations containing same |
US4317768A (en) * | 1977-10-14 | 1982-03-02 | Labaz | Dihydropyridine derivatives as stabilizers for vinyl chloride polymers |
US5280047A (en) * | 1991-11-18 | 1994-01-18 | G. D. Searle & Co. | 2-(4-substituted)phenylmethylene derivatives and methods of use |
US5571827A (en) * | 1990-03-13 | 1996-11-05 | Sepracor Inc. | Methods and compositions for treating hypertension, angina and other disorders using optically pure s(-) nitrendipine |
US5665740A (en) * | 1993-12-10 | 1997-09-09 | Bayer Aktiengesellschaft | Isopropyl 2-methoxyethyl 4-(2-chloro-3-cyano-phenyl)-1, 4-dihydro-2,6-dimethyl-pyridine-3,5-dica rboxylate |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1409865A (en) * | 1973-02-13 | 1975-10-15 | Science Union & Cie | Dihydropyridines derivatives their preparation and pharmaceu tical compositions containing them |
DK152285C (da) * | 1975-07-02 | 1988-10-10 | Fujisawa Pharmaceutical Co | Analogifremgangsmaade til fremstilling af 1,4-dihydropyridinderivater |
SE7910521L (sv) * | 1979-12-20 | 1981-06-21 | Haessle Ab | Nya 2-metyl-6-substituerade-4-(2,3-disubstituerad fenyl)-1,4-dihydropyridin-3,5-diestrar med hypotesiva egenskaper, samt forfarande for deras framstellning, och farmaceutiska beredningar innehallande desamma |
JPS60120861A (ja) * | 1983-12-02 | 1985-06-28 | Otsuka Pharmaceut Co Ltd | ジヒドロピリジン誘導体 |
IE57810B1 (en) * | 1984-03-27 | 1993-04-21 | Delagrange Lab | 1,4-dihydropyridine derivatives,their preparation and their use |
JPS6143165A (ja) * | 1984-08-07 | 1986-03-01 | Otsuka Pharmaceut Co Ltd | ジヒドロピリジン誘導体の製造法 |
PT657432E (pt) * | 1993-12-10 | 2003-07-31 | Bayer Ag | 1,4-di-hidropiridinas fenil-substituidas com actividade cerebral |
DE19727350C1 (de) * | 1997-06-27 | 1999-01-21 | Bayer Ag | Verfahren zur Herstellung von Nifedipin |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE1923990C3 (de) * | 1969-05-10 | 1978-11-23 | Bayer Ag | Verfahren zur Herstellung von N-substituierten M-Dihydropyridin-S.S-dicarbonsäureestern |
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1971
- 1971-04-10 DE DE2117572A patent/DE2117572C3/de not_active Expired
-
1972
- 1972-03-09 CH CH1159775A patent/CH571493A5/xx not_active IP Right Cessation
- 1972-03-09 CH CH345972A patent/CH571491A5/xx not_active IP Right Cessation
- 1972-03-27 AU AU40454/72A patent/AU459338B2/en not_active Expired
- 1972-04-05 SU SU1768162A patent/SU431671A3/ru active
- 1972-04-05 SU SU1932086A patent/SU475771A3/ru active
- 1972-04-06 BG BG23739A patent/BG20106A3/xx unknown
- 1972-04-06 FI FI947/72A patent/FI55187C/fi active
- 1972-04-06 BG BG23740A patent/BG19374A3/xx unknown
- 1972-04-06 BG BG23738A patent/BG19595A3/xx unknown
- 1972-04-06 BG BG20165A patent/BG20353A3/xx unknown
- 1972-04-07 NL NLAANVRAGE7204694,A patent/NL170140C/xx not_active IP Right Cessation
- 1972-04-07 AT AT301772A patent/AT316552B/de not_active IP Right Cessation
- 1972-04-07 DD DD162141A patent/DD104519A5/xx unknown
- 1972-04-07 NO NO1191/72A patent/NO133711C/no unknown
- 1972-04-07 DK DK172272A patent/DK132321C/da not_active IP Right Cessation
- 1972-04-07 ZA ZA722355A patent/ZA722355B/xx unknown
- 1972-04-07 US US00242238A patent/US3799936A/en not_active Expired - Lifetime
- 1972-04-07 JP JP3450672A patent/JPS5527054B1/ja active Pending
- 1972-04-07 IE IE455/72A patent/IE36947B1/xx unknown
- 1972-04-07 LU LU65129D patent/LU65129A1/xx unknown
- 1972-04-08 PL PL1972154621A patent/PL84571B1/pl unknown
- 1972-04-08 PL PL1972175387A patent/PL92407B1/pl unknown
- 1972-04-08 ES ES401615A patent/ES401615A1/es not_active Expired
- 1972-04-10 RO RO197270489A patent/RO59959A/ro unknown
- 1972-04-10 CA CA139294A patent/CA925513A/en not_active Expired
- 1972-04-10 BE BE781879A patent/BE781879A/fr not_active IP Right Cessation
- 1972-04-10 HU HUBA2728A patent/HU165875B/hu unknown
- 1972-04-10 SE SE7204607A patent/SE371824B/xx unknown
- 1972-04-10 GB GB1646372A patent/GB1331405A/en not_active Expired
- 1972-04-10 RO RO197279438A patent/RO63113A/fr unknown
- 1972-04-10 IL IL7239170A patent/IL39170A/xx unknown
- 1972-04-10 CS CS2378A patent/CS177821B2/cs unknown
- 1972-04-10 CS CS3558A patent/CS177846B2/cs unknown
- 1972-04-10 FR FR7212513A patent/FR2132831B1/fr not_active Expired
Cited By (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3920823A (en) * | 1972-03-06 | 1975-11-18 | Bayer Ag | Use of unsymmetrical esters of n-substituted 1,4-dihydropyridine 3,5-dicarboxylic acid as cardio-vascular agents |
US3917619A (en) * | 1972-03-06 | 1975-11-04 | Bayer Ag | 2-Amino-4,5-dihydropyridine derivatives |
US4001258A (en) * | 1972-03-06 | 1977-01-04 | Bayer Aktiengesellschaft | 2-amino-1,4-dihydropyridine derivatives |
US3939171A (en) * | 1972-03-06 | 1976-02-17 | Bayer Aktiengesellschaft | 2-Amino-1,4-dihydropyridine derivatives |
US3935223A (en) * | 1972-03-06 | 1976-01-27 | Bayer Aktiengesellschaft | 2-Amino-1,4-dihydropyridine derivatives |
US3887558A (en) * | 1972-03-06 | 1975-06-03 | Bayer Ag | Process for producing 2,6-diamino -1,4- dihydro-3,5-pyridine-dicarboxylates and derivatives thereof |
US3988458A (en) * | 1972-03-06 | 1976-10-26 | Bayer Aktiengesellschaft | Bicyclic derivatives of 1,4-dihydropyridine 3,5-carboxylic acid esters |
US3876646A (en) * | 1972-03-06 | 1975-04-08 | Bayer Ag | 2-amino-4,5-dihydropyridine derivatives |
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US3989708A (en) * | 1972-08-31 | 1976-11-02 | Bayer Aktiengesellschaft | 2-Amino-1,4-dihydropyridine derivatives |
US3862162A (en) * | 1972-08-31 | 1975-01-21 | Bayer Ag | Certain-2-amino-1,4-dihydro-4-phenyl-6-lower alkyl (or phenyl)-3-pyridinecarboxylates |
US3905983A (en) * | 1972-09-30 | 1975-09-16 | Bayer Ag | 3,5,6-Tricarboxy- and 2,3,5,6-tetracarboxy-1,4-dihydropyridine derivatives |
US3857849A (en) * | 1973-02-28 | 1974-12-31 | Bayer Ag | 2-amino-1,4-dihydropyridine derivatives |
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US5571827A (en) * | 1990-03-13 | 1996-11-05 | Sepracor Inc. | Methods and compositions for treating hypertension, angina and other disorders using optically pure s(-) nitrendipine |
US5280047A (en) * | 1991-11-18 | 1994-01-18 | G. D. Searle & Co. | 2-(4-substituted)phenylmethylene derivatives and methods of use |
US5665740A (en) * | 1993-12-10 | 1997-09-09 | Bayer Aktiengesellschaft | Isopropyl 2-methoxyethyl 4-(2-chloro-3-cyano-phenyl)-1, 4-dihydro-2,6-dimethyl-pyridine-3,5-dica rboxylate |
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